A retrospective cohort study of maternal and newborn outcomes and maternity care provider mix in rural British Columbia

Over 40,000 babies are born each year in BC; approximately 15,000 to mothers who live outside the core urban areas of the province. A wave of obstetric service closures over the past ten years has resulted in increasing numbers of pregnant women having to travel long distances to access maternity services or having to relocate to a referral centre in their third trimester. Recent research from BC shows that women who live in communities without local maternity services experience more stress and anxiety during pregnancy due to the financial and emotional hardship incurred by leaving their communities to access services. Babies of women from BC who live further away from services are also more likely to experience negative outcomes, such as stillbirth or neonatal death.

The goal of of this study is to determine how the composition of rural maternity services relates to maternal and newborn outcomes, taking into consideration the characteristics and risk profile of childbearing women.

Using data from British Columbia Perinatal Services, and detailed information about the number and mix of maternity care providers (family physicians, obstetricians, midwives etc.) in each rural hospital catchment, Dr. Stoll will study the outcomes of mothers and babies over a ten-year period (2000 – 2010). In addition, she will examine whether the proportion of women who give birth in their home community as opposed to a referral hospital, changes with different maternity care provider compositions. She will describe how the number and mix of maternity care providers in rural communities relate to population outcomes using quantitative analysis.

Findings from this study will contribute to formulating optimal models of maternity care delivery for rural communities in BC and across Canada.

Exploring how the process of genetic counselling influences outcomes for individuals with serious mental illnesses

Serious mental illness (SMIs), like schizophrenia, schizoaffective, and bipolar disorder, impact almost one million Canadians. The cause of SMIs are extremely complex. While research clearly demonstrates a genetic component, multiple genes are thought to interact with environmental factors to cause the illnesses. Until recently, knowledge on the genetic and environmental causes of SMIs have not been addressed in standard medical care. However, emerging evidence suggests that genetic counselling (GC) can provide important and far-reaching benefits for patients, including decreased internalized stigma and increased perceived control. Anecdotal evidence also suggests that GC may improve treatment adherence, which represents a serious and significant challenge in illness management for persons with SMIs.

This study will explore and identify the aspects of the GC process that most effectively and positively influence outcomes, specifically medication adherence, for persons with SMIs.

Males and females with schizophrenia, schizoaffective, or bipolar disorder will be invited to participate in two interviews — one conducted prior to receiving GC, and the other within two weeks of receiving GC. Interviews will explore patients’ perceptions of SMIs and psychotropic medication; psychosocial and informational needs; and expectations about GC. The nature of the patient-counsellor interaction; the depth/type of information provided; and the effectiveness of different counselling approaches in relation to patients’ needs and expectations will also be examined. All interviews will be audiotaped, transcribed verbatim, and analyzed using the constant comparative method and coding procedures of Grounded Theory.

The ultimate goal of Semaka’s study is to develop a theoretical model that explains how GC influences patient outcomes, specifically treatment adherence, which will inform the development of evidence-based clinical practice guidelines for the routine delivery of GC for SMIs.

Response of the host interactome to Campylobacter jejuni invasion

The ability of bacterial pathogens to invade and survive within the cells of a human host is governed by the interplay between host and bacterial factors. Under these conditions, both host and pathogen generate multiple mediators that, through interactions with other proteinous factors alter the intercellular host environment. These interactions govern the development of disease and are largely mediated by the physical association of proteins and the generation of protein complexes. Currently, our understanding of protein complexes and the remodeling of complexes in response to certain bacterial pathogens such as the leading foodborne cause of gastroenteritis, Campylobacter jejuni, are incomplete. This incomplete understanding of the dynamic changes in the host in response to bacterial infection is due multiple shortcomings associated with traditional approaches for investigating protein interactions.

Ideally, to better understand how C. jejuni interacts and survives in the human host, a greater understanding of the dynamics of protein complexes are required. In his analysis, Dr. Scott aims to understand the molecular changes in response to C. jejuni infection and to further develop the use of protein correlation profiling to study protein interactions.

Recently, it was demonstrated that the use of size exclusion chromatography, metabolic protein labeling and mass spectrometry provided an ideal platform to study the interaction of complexes under multiple conditions (Kristensen et al, Nat. Meth. 2012). By examining the C. jejuni infection of human cells through these imagings techniques, the mechanism by which this pathogen develops can be further understood.

The information garnered through Dr. Scott’s research can be incorporated into studies aimed at using traditional targeted approaches to understand how protein interactions contribute to changes in the host as a result of bacterial agents.

Post-translational modifications as a virulence strategy of diarrheagenic E. coli

With an estimated 1.5 million fatal cases among children and about 2 billion cases total annually, diarrheal diseases are a significant cause for morbidity and mortality worldwide. Enteropathogenic and enterohemorrhagic E. coli (EPEC/EHEC) are two forms of diarrheagenic E. coli that cause these diseases. EPEC provokes potentially fatal infantile diarrhea and EHEC triggers severe diarrhea, which can progress to fatal renal failure. Both pathogens infect epithelial cells of the host intestine. They utilize a sophisticated delivery system, the type III secretion system, to inject specialized effector proteins into the host cytosol. Once translocated, these effectors trigger signaling events to subvert host cell functions and cause disease. However, only little is known about respective host targets and mechanistic details.

Dr. Scholz’s research aims to clarify if and how EPEC/EHEC utilize effectors to interfere with the host posttranslational modification (PTM) machinery and thus with host signaling to promote disease. His research will represent the first comprehensive analysis of the role of PTMs in EPEC/EHEC pathogenesis and will provide new strategies for therapeutic approaches against bacterial pathogens.

Throughout his study, Dr. Scholz plans to pursue identified host targets, elucidate the mechanistic details of this effector-host target interplay and clarify its consequences for pathogenesis. Having already established a highly efficient, reliable and comprehensive screening approach for phosphorylation, a common and pivotal PTM in host signaling, he further plans to employ similar strategies to target also other types of PTMs, such as ubiquitination, and define their role during EPEC/EHEC infection.

Unique contributors to caregiver well-being across neurodegenerative diseases that present with dementia

Five million new cases of dementia are diagnosed every year worldwide. These diagnoses disrupt home environment patterns and relationships and cause  repercussions on families. Accordingly, dementia caregivers experience higher stress than other groups and face diverse care demands. Existing literature suggests dementia presentation may impart different caregiver challenges: cognition in Alzheimer’s disease (AD); delusions in Dementia with Lewy Body (DLB); and neuropsychiatry in Parkinson’s disease associated dementia (PDD). Inconsistencies in studies comparing dementia caregivers make it difficult to draw clear conclusions. First, caregiver definitions are inconsistent. Second, caregiver well-being is under-represented. Third, disease pathology and associated-dependencies place differential demands on caregivers, which has yet to be examined in a comparative framework.  

The proposed research will address this gap by comparing dementia-related symptoms that contribute to caregiver well-being[LL1] . The aim is to determine the unique profile of contributors to caregiver well-being in neurodegenerative diseases (i.e. AD, DLB, PDD) present with dementia[LL2] .

It is expected dementia presentations and associated factors will differentially impact caregiver well-being. Dr. Roland will administer questionnaires to evaluate well-being (life-satisfaction, depression), burden and coping in caregivers. Focus groups will bring together a range of dementia caregivers from three groups (AD, DLB, PDD) to explore group norms and diverse experiences. Subsequent interviews will further explore the issues pertinent to caregiver well-being. This novel research will identify the unique profile of caregiving factors within a comparative framework. This is important since different presentations of dementia have discrete long-term implications for caregiver psychosocial outcomes.

Relevant knowledge gained from Dr. Roland’s research will inform resources targeted to reduce stressors and support care needs

Screening and development of molecules targeting presynaptic SNARE protein-protein interactions as novel pharmacological strategy in schizophrenia and other mental illnesses

Screening and development of molecules targeting presynaptic SNARE protein-protein interactions as novel pharmacological strategy in schizophrenia and other mental illnesses Schizophrenia is one of the major disabling mental disorders with a worldwide prevalence of about one percent. Although the cause  of schizophrenia remains unclear, converging data indicate that dysfunctions altering neurotransmitter levels in the synaptic cleft, the tiny space between nerve cells in which nerve impulses are conducted, might be at the core of this disorder. In presynaptic cells, neurotransmitter release is governed by SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor).  Findings in the schizophrenic postmortem brain have revealed increased SNARE protein-protein interactions, which may explain the unbalanced neurotransmitter levels in schizophrenia, and reduced SNARE complexes in antipsychotic-treated patients. In accordance, genetic differences in SNARE-coding genes have been associated with schizophrenia.

Despite the growing evidence involving presynaptic dysfunction in mental illnesses, no attempts have been made to develop a pharmacological approach targeting the SNARE complex. Furthermore, the sole active agent against SNARE proteins, Botox cannot be used due to its irreversible, and lethal effects, presenting a challenge to finding SNARE-interfering compounds and pharmaceutically treating schizophrenia.

Against this background, the objective of Dr. Ramos-Miguel’s clinical research project is to find SNARE-interfering compounds, and further address their potential benefits in the pharmacological management of schizophrenia.

To meet this goal, an  agreement involving UBC, the Centre for Drug Research and Development (CDRD), and Roche-Canada, will allow Dr. Ramos-Miguel’s team to  screen the company’s largest library, containing more than one million compounds. Additionally, an immunoassay-derived method has been automated for high throughput screening of compounds modifying SNARE interactions. This assay successfully screened the CDRD 26,000-compound library, and identified at least two SNARE “inhibitors”. Further hits from the screening project will be subjected to a number of preclinical tests, including immunological, electrophysiological, toxicological and behavioral assays.

Identification of SNARE-interfering substances may have potential to improve pharmacological treatment of schizophrenia through a completely novel strategy.

Brain strain: Effect of autonomic dysreflexia on cerebral blood flow and cognition

Spinal cord injury (SCI) is a devastating chronic condition resulting not only in paralysis but severe autonomic cardiovascular dysfunction. In fact, cardiovascular disease is the leading cause of death in those living with SCI. Autonomic dysreflexia (AD) is a life-threatening condition characterized by episodes of extreme hypertension accompanied by pounding headaches, confusion, seizures, strokes and even death. Despite the high incidence of AD in individuals with cervical or high thoracic SCI and the negative impact this condition has on on the brain, there has been no prior studies examining the relationship between AD and cognition or cerebral blood flow.

Dr. Phillips’ research comprehensively examines cerebral blood flow during progressive AD and relates chronic AD severity to cognitive function. The vast majority of men with SCI experience sexual dysfunction and difficulty with ejaculation. Vibrostimulation is a standard medical procedure that helps with obtaining sperm for the purpose of family-planning. However, this procedure elicits AD in 96 percent of individuals with SCI above T6 and requires careful monitoring. Nonetheless, vibrostimulation offers a unique and ideal model through which it is possible to study the influence of AD on a number of cerebrovascular parameters.

As pilot data for this proposal, Dr. Phillips recorded spontaneously occurring AD bouts in individuals with SCI. In Project 1, Dr. Phillips will examine and measure cerebral blood flow during AD (induced by vibrostimulation) using Transcranial Doppler tests in the middle and posterior cerebral arteries, as well as a newly-developed volumetric technique using duplex ultrasound of the internal carotid and vertebral arteries. In Project 2, Dr. Phillips will examine the relationship between severity of AD (from 24 hour blood pressure monitoring) and cognitive function in SCI.

Ultimately, Dr. Phillips’ study will greatly contribute to the understanding of the cerebrovascular and cognitive effects of AD.

A prospective investigation of the relationship between depressed mood, sexual pleasure and desire in women with Sexual Interest/Arousal Disorder (SIAD)

Sexual Interest/Arousal Disorder (SIAD) is the most widespread sexual complaint in women, with reduced pleasure during sexual activity as one of the most common features. SIAD is associated with elevated depression symptoms, relationship distress, and presents a significant health care burden. Although low sexual desire is a common symptom of depression, little is known about how less severe depressed mood influences sexual desire in women who do not have depression.

The goal of Dr. Paterson’s study is to clarify how a depressed mood and reduced sexual pleasure and desire interact in women with SIAD.

Two studies will compare premenopausal women with SIAD but without depression to a healthy control group. In the first study, participants will complete electronic daily diaries for one month, in which they will provide ratings of sexual desire, sexual pleasure experienced with a partner and depressed mood. It is expected that women with SIAD will report less sexual desire, greater depressed mood, and less sexual pleasure than healthy women, and that the depressed mood will contribute to low desire by decreasing both the experience and memories of sexual pleasure. In the second study, women seeking help for SIAD and who also have depressed mood will receive mindfulness-based cognitive-behavioural therapy in a group format. This therapy will target sexual desire and depressed mood, and is expected to significantly improve both problems.

The results will help improve treatment options for women with SIAD by also demonstrating the importance of addressing depressed mood.

A preventive parenting program for family reunification

Out-of-home care accomodates children who face serious distruptions in their family environment, including severely impaired, abusive, and/or neglectful parenting, and elevated behavioural and emotional problems in children. The most common and desired goal for children in out-of-home care is to achieve a timely and safe family reunification (FR), i.e. the process of returning children to their families of origin. The risk for developing or exacerbating mental health problems that impacts behavioural conduct in these children increases relative to the number of significant disruptions (e.g. multiple placements) they experience while waiting for FR. There are two significant impediments to achieving a well-timed and stable FR: (1) children’s conduct problems and (2) parents’ lack of confidence or skills in managing their child’s behaviour. Though decades of research suggests that parent management training programs can significantly improve parenting skills and self-efficacy while effectively treating and/or preventing conduct problems in young children, there is no existing research investigating whether these programs may be effective with birth parents of children in out-of-home care, specifically for the purpose of FR.

Accordingly, Dave Pasalich’s research will examine the feasibility and efficacy of a parenting program for FR.

Through intervention, Pasalich will focus on improving parent-child interactions between young children (aged 3 to 7) in out-of-home care and their birth parents.

It is envisioned that the short-term effects of the parenting program on improving the quality of the parent-child relationship, parenting, and reducing conduct problems in children, will (1) increase the likelihood of achieving FR; (2) decrease the time taken to achieve FR; and (3) decrease the need for these children to re-enter the out-of-home care system at a later stage, or at least delay the need for re-entry.